alpha-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication

作者：Aulic Suzana; Masperone Lara; Narkiewicz Joanna; Isopi Elisa; Bistaffa Edoardo; Ambrosetti Elena; Pastore Beatrice; De Cecco Elena; Scaini Denis; Zago Paola; Moda Fabio; Tagliavini Fabrizio; Legname Giuseppe^*

来源：Scientific Reports, 2017, 7(1): 10050.

DOI：10.1038/s41598-017-10236-x

The precise molecular mechanism of how misfolded alpha-synuclein (alpha-Syn) accumulates and spreads in synucleinopathies is still unknown. Here, we show the role of the cellular prion protein (PrPC) in mediating the uptake and the spread of recombinant alpha-Syn amyloids. The in vitro data revealed that the presence of PrPC fosters the higher uptake of alpha-Syn amyloid fibrils, which was also confirmed in vivo in wild type (Prnp(+/+)) compared to PrP knock-out (Prnp(-/-)) mice. Additionally, the presence of alpha-Syn amyloids blocked the replication of scrapie prions (PrPSc) in vitro and ex vivo, indicating a link between the two proteins. Indeed, whilst Pr-PC is mediating the internalization of alpha-Syn amyloids, PrPSc is not able to replicate in their presence. This observation has pathological relevance, since several reported case studies show that the accumulation of alpha-Syn amyloid deposits in Creutzfeldt-Jakob disease patients is accompanied by a longer disease course.

• 出版日期2017-8-30